Needleless injector with shock absorbing means between ram and piston

ABSTRACT

A needleless injector has a syringe body having an opening at one end, a piston housed within the syringe body for urging a liquid within the syringe body through the opening and a ram for driving the piston. A shock absorbing component is provided for reducing an initial transfer of force from the ram to the piston. The initial rate of pressure increase on the liquid is reduced, thereby controlling the rate of collapse of gas bubbles in the liquid.

BACKGROUND TO THE INVENTION

Needlefree injectors are used as an alternative to needle-typehypodermic injectors for injecting liquid drugs through the epidermisand into the underlying tissues. The usual form of construction for sucha device is a syringe having a small discharge orifice which is placedin contact with the skin, and through which the drug is injected at asufficiently high speed to penetrate the skin of the patient. The energyrequired to pressurise the drug may be derived from a compressed coilspring, compressed gas, explosive charge or some other form of storedenergy.

There are a number of different ways in which the energy may beconverted from the stored form into pressure in the liquid. These mayinclude rupturing a seal, so allowing gas to escape from a canister andcausing pressure to build up behind a piston which pressurises the gas.Alternatively, a gas may cause a ram to accelerate across a gap, priorto impacting on the back of a piston.

Whichever method is used to pressurise the fluid, it is important thatthe peak pressure in the fluid is achieved quickly enough to enable theinitial ‘pulse’ of fluid to have a sufficiently high pressure topenetrate the skin. The remainder of the fluid may be delivered at asimilar pressure, or a substantially lower pressure, depending on theconfiguration of the device. Some needle free devices are designed to befilled by the user, whilst others are prefilled, either by the drugmanufacturer or by a third party. In either case, it is important thatthe contents of the drug capsule are predominantly free from bubbles,especially in the nozzle area.

SUMMARY OF THE INVENTION

The invention is based on the recognition that a very rapid rise inpressure in the drug can give rise to a rapid collapse of the bubbles inthe drug. This bubble collapse, if it occurs quickly enough, can causeshock waves within the capsule, which can give rise to extremely highlocalised stresses. These stresses can sometimes cause the capsule tofail during this initial pressure peak, which is likely to result in anincomplete injection.

The inventors have recognised that it would therefore be beneficial toensure that the collapse of any bubble that may be present in thecapsule (either because of the filling process, or because of any gasthat may come out of the drug solution due to changes in temperature,pressure etc.) is in a slow controlled manner. It has been found that,depending on the material and geometry of the capsule, bubbles greaterthan around 0.5-1 μl can increase the probability of the capsulebreaking.

It has also been found that the key factor giving rise to these shockwaves is the initial rate of pressure increase. The peak pressure in thefluid may be around 200-400 Bars, and yet by slowing the rate ofpressure increase from atmospheric pressure to around 20 Bars still hasa dramatic effect on reducing the shock wave generation, even if theremainder of the pressure increase occurs at the same rate aspreviously.

The invention provides a method of preventing a: collapsing bubble fromcausing a needle free injector capsule to break, and comprises the stepof causing the bubble to collapse in a slower, controlled mannerimmediately prior to the normal injection cycle, without changing thepeak value or the shape of the remainder of the pressure profile. Theinvention also provides an apparatus for this purpose.

According to a first aspect of the invention, there is provided aneedleless injector comprising:

-   -   a syringe body having an opening at one end;    -   a piston housed within the syringe body for urging a liquid        within the syringe body through the opening;    -   a ram for driving the piston;    -   means for applying a force to the ram; and    -   shock absorbing means for reducing an initial transfer of force        from the ram to the piston.

This apparatus provides reduction of the initial force applied to theram, so that the initial rate of pressure increase on the liquid isreduced, thereby controlling the rate of collapse of gas bubbles in theliquid.

The shock absorbing component may be provided in the gap across whichthe ram is accelerated prior to impact with the piston.

The shock absorber may comprise a cylinder, in which the ram (or aportion thereof) is slidably received. This cylinder can be closed atone end, and the closed end lies adjacent the piston. The ram is thenreceived adjacent the open end of the cylinder before application offorce to the ram. In this way, shock absorbing is achieved by drivingthe ram into a cylinder. Preferably, the ram is also slidably receivedin the cylinder with a fluid tight fit, so that as the ram progressesinto the cylinder, a volume of gas trapped in the cylinder iscompressed, thereby providing a gradually increasing force on thepiston.

In another arrangement, the cylinder can be open at both ends. Theinternal opening of the cylinder may have a constant internal diameter,or else the internal opening of the cylinder may have at least twointernal diameters, a first internal diameter at an end of the cylinderfor cooperation with the ram, and a second smaller internal diameter.

This provides a step in the internal profile, which provides a localpressure peak which results in a low initial pressure for ensuringbubble collapse. The internal opening of the cylinder can have threeinternal diameters, a third internal diameter at an end of the cylinderfor cooperation with the piston, the third internal diameter beinggreater than the second internal diameter. The third internal diametercan-be equal to or greater than the diameter of the ram, so that thissection of the component does not increase the frictional resistance tothe ram, but provides length over which the initial pressure continuesto act before impact of the ram with the piston.

The cylinder may have a length of between 1 mm and 5 mm, and this shortinitial absorbing of the movement of the ram acts to reduce the appliedforce. The shock absorber may comprise a different compressible member.

The invention also provides a method of delivering liquid from aneedleless injector syringe which comprises a piston housed within asyringe body and a ram for driving the piston thereby causing liquid tobe driven out of the syringe, the method comprising:

-   -   applying a force profile to the ram;    -   during a first stage of the delivery cycle, at least partially        absorbing the force applied to the ram and applying the reduced        force to the piston; and    -   during a second stage of the delivery cycle, transferring        substantially the full force applied to the ram to the piston.

This method provides a two-stage process, with damping ill the firstprocess only.

BRIEF DESCRIPTION OF THE DRAWINGS

An example of the invention will now be described in detail withreference to the accompanying drawings, in which:

FIG. 1 shows a known needleless injector;

FIG. 2 shows a modification to the injector of FIG. 1 using a firstexample of shock absorbing component of the invention;

FIG. 3 shows a second example of shock absorbing component of theinvention;

FIG. 4 shows pressure plots to illustrate the effect of the component ofFIGS. 2 and 3;

FIG. 5 shows a third example of shock absorbing component of theinvention;

FIG. 6 shows a fourth example of shock absorbing component of theinvention;

FIG. 7 shows pressure plots to illustrate the effect of the component ofFIG. 6;

FIG. 8 shows a fifth example of shock absorbing component of theinvention; and

FIG. 9 shows pressure plots to illustrate the effect of the component ofFIG. 8.

DETAILED DESCRIPTION

FIG. 1 shows a known needleless injector, comprising a syringe body inthe form of a cartridge 103 having an opening 106 at one end. A piston104 is housed within the cartridge 103 for urging a liquid 105 withinthe cartridge through the opening 106. A ram 111 is provided for drivingthe piston, and an arrangement is provided for applying a force to theram 111.

The are numerous possible ways of applying force to the ram. In theexample shown, the injection force is provided by a compressed gasspring. This is in the form of a cylinder 130 which is closed at itsupper end and which contains gas, typically air, under a pressure whichis typically in the range 5.5 MPa (800 psi) to 22 MPa (3000 psi). Thecylinder houses the ram 111. The end of the ram 111 has a frustoconicalportion 131 and a flange 132 between which is situated an O-ring seal133. Prior to use, the ram 111 is held in the illustrated position by alatch 108 engaging in a groove in the ram, the upper surface of thegroove forming a cam surface 109.

The lower end of the cylinder 130 has an outwardly directed flange 130a, which enables the cylinder to be held by crimping the flange 130 abeneath an outwardly directed flange 140 a at the upper end of acoupling 140. The sleeve 102 is formed of an upper sleeve portion 102 awithin which the cylinder is situated, and a lower sleeve portion 102 b.The sleeve portion 102 b is connected to the coupling by theinterengaging screw threads 141 formed on the inner and outer walls ofthe sleeve portion 102 b and coupling 140 respectively.

The ram arrangement, of the compressed gas cylinder 130 and the ram 111,are assembled to form a first component which is subsequently attachedto the cartridge assembly.

The injector contains the medicament cartridge 103 in which the piston104 is slidingly and sealingly located therein, in contact withmedicament 105. As considered from the upper end of FIG. 1, the pistonmay comprise a cylindrical portion, a larger diameter cylindricalsealing portion, and a frusto-conical portion. The opening 106 is sealedby a resilient seal 134 which is held in place by a seal carrier 135.The seal carrier 135 is connected to the lower sleeve portion 102 b by afrangible joint 136.

As a precaution against accidental firing, a tear-off band 137 isprovided as the lower part of the upper sleeve portion 102 a. The loweredge of the tear-off band 137 bears against a ring 142 which is bondedto the exterior surface of the coupling 140 or (not shown) formedintegrally therewith. The function of the ring is to prevent downwardmovement of the sleeve portion 102 a relative to the coupling 140, forso long as the tear-off band 137 is present. Accordingly, the ring 142need not extend completely around the periphery of the coupling, andcould be replaced by one or more separate elements.

An annular space 138 is formed in the inside wall of the sleeve 102,where the sleeve is adjacent the cylinder 130, and the space is filledwith a damping grease (indicated diagrammatically by a succession ofblack bands), so that the grease is in intimate contact both with thesleeve 102 and the cylinder 130. It should be noted that although adefined annular space is convenient from the point of view of providinga particular location for the grease, it could be omitted and the greasesimply smeared over all or part of the outside of cylinder 130 and/orinside of sleeve 102.

When the embodiment of FIG. 1 is to be operated, the user snaps off theseal carrier 135 at the frangible joint 136, which takes the seal 134with it and exposes the orifice 106. The user then removes the tear-offband 137, and grasping the upper part of the sleeve 102 urges theorifice against the skin which is to be injected. This moves the uppersleeve portion 102 a downwardly, with respect to the lower sleeveportion 102 b. This brings aperture 139 in the wall of the upper sleeveportion 102 a into alignment with the latch 108, which is thus able tomove sideways into the aperture under the influence of the force of thegas within the cylinder 130 acting on the latch via the cam surface 109formed in the ram 111. The injector is thus caused to fire. As aprecaution, in case the latch fails to move under the influence of thecam surface 109, an auxiliary cam surface 143 is provided on the insideof the sleeve portion 102 a. The resulting recoil is damped by thedamping grease.

As discussed above, gas bubbles within the liquid 105 must be avoided,because the rapid increase in pressure in the liquid after firing canresult in any such bubbles affecting the injection performance.

As shown in FIG. 2, the invention provides a shock absorbing component150 between the ram and the piston for reducing an initial force appliedto the ram. The component fills the gap across which the ram isaccelerated.

In one embodiment of the invention shown in FIG. 2, a blind tube is usedas the shock absorbing component 150, which is an interference fit witha portion of the ram 111 that accelerates towards the piston. The blindtube comprises a hollow cylinder which is closed at one end, the closedend lying adjacent the piston, and the ram is received adjacent the openend of the cylinder before application of force to the ram (as in FIG.2).

The component 150 can be formed from PTFE, and is then machined to formthe desired shape. It may be formed integrally with the piston 104.Alternatively, other high density and resilient materials may be used,such as high density polyurethane (“HDPE”), which can be moulded.

In the example shown, the cylinder 150 rests behind the piston 104 (ormay be formed integrally with it as mentioned above), and is in contactwith it. As the ram 111 accelerates, two phenomena occur. Firstly,friction between the ram 111 and the cylinder 150 causes a force to beapplied to the piston 104. This force is very much smaller than thesubsequent impact force between the ram 111I and the piston 104.Secondly, the interference fit between the portion of the ram 111 andthe cylinder 150 causes a gas tight seal. Therefore, as the ram 111moves down inside the cylinder 150, the pressure in the cylinderincreases, resulting in a gradually increasing force to be applied tothe piston 104 by the cylinder 150. As this force increases, the piston104 is moved forward slightly, which causes any bubble to be compressed.Typically, in one embodiment of the invention, the ram acceleratesacross a gap 152 of 3 mm, in about 200 μs. This causes a substantiallysteady increase in pressure from 0 to around 1-5 Mpa over this time.This causes a gradual collapse of the bubble over this period, from itsoriginal size, to a tiny fraction (for example {fraction (1/20)}) of itssize. Furthermore, if the bubble is in, or very close to, the opening ofthe cartridge 103, it is likely to be pushed out of the orifice.

The effect of this is that, when the ram 111 impacts on the blind(closed) end of the cylinder 150, which in turn is in contact with theback of the piston 104, there will be no bubble present in the capsuleof a significant size. This means that, despite the extremely rapid risein pressure caused by this impact, and necessary to penetrate the skin,there will not be high localised stresses and shock waves caused by thecollapse of large bubbles. The gradual collapse of the bubble caused bythe increase in pressure to around 1-5 MPa, means that any bubblepreviously smaller than 10 μl, will be below the critical size of 0.5 μlat the time when the ram impacts the piston.

In an alternative arrangement, the component 150 can be seated over theend of the ram 111, and thus form part of the ram arrangement. Forexample, the component can be placed over an end of the ram 111 whichprojects beyond an end face of the assembled ram arrangement. This endface can then act as a stop to limit the positioning of the component150 over the ram 111. When the ram is released, the component 150 moveswith the ram inside the cartridge 103 until it strikes the piston 104.Only then is the shock absorbing function of the component 150 used.

This design enables the component to be introduced as a modificationwhich does not require any change to an existing ram arrangement or tothe cartridge assembly design.

The shock absorbing component reduces the initial rate of pressureincrease within the drug-containing capsule. There may be a slightreduction in the peak pressure with which the drug is expelled, andvarious modifications to the shock absorbing component are possible toachieve a desired combination of the initial pressure profile and thepressure profile during the actual injection cycle.

For example, the degree of interference between the inner surface of thecylinder 150 and the ram may be altered to vary the reduction in initialpressure. For example, for a ram diameter of 4.0 mm, an inner diameterof the cylinder may typically be 3.77 mm, or it may be reduced to 3.6 mmto introduce greater frictional resistance. A typical tolerance may be0.03 mm.

The design of shock absorbing component above has a closed end so that asealed chamber is defined by the shock absorbing component incombination with the ram 111. However, the frictional interference alonemay be sufficient. FIG. 3 shows a shock absorbing component 150 which isopen at both ends. The amount of frictional resistance and the lengthcan then be chosen to achieve the desired pressure profile.

FIG. 4 shows comparative pressure profiles for an injector-with no shockabsorbing component (plot 200), with the closed cylinder of FIG. 2 (plot202) and two versions of the component of FIG. 3 of different lengths(plots 204-length 4.5 mm and 206-length 5 mm). As shown, the presence ofthe shock absorbing component in each case provides the pressure region210 which provides gradual bubble collapse, but the peak pressure surgeat impact of the ram with the piston varies in the different designs.

It has been found (from studying fired devices) that there issignificant deformation of the back of the piston 104 from the impactwith the ram. Clearly, if such deformation can be reduced (which absorbsenergy) this can provide an increased pressure peak at the point ofimpact of the ram with the piston (once the shock absorbing function hasbeen completed).

FIG. 5 shows a modification in which a metal end cap 220 is placed overthe opening on the piston side of the shock absorber component. This isfound to increase the peak pressure at the point in time when contact ismade between the ram and the end cap. However, this increase in peakpressure is accompanied by a narrowing of the pressure peak, which maynot be desirable.

A further modification combines different degrees of frictionalresistance within cylindrical bore. FIG. 6 shows a shock absorber havinga closed end (as in FIG. 2) and in which two different internaldiameters d1 and d2 are provided. The component is initially providedwith a bore of diameter d2, and an additional counterboring stepprovides the increased internal diameter of d1 to a desired depth.Taking the example of the 4.0 mm diameter ram, d1 can equal 3.77 mm andd2 can equal 3.6 mm. The depth of the counterbore will of courseinfluence the pressure profile characteristics. It will be seen that theheight of the step between internal bore diameters is exaggerated inFIG. 6.

FIG. 7 shows comparative pressure profiles for an injector with no shockabsorbing component (plot 200), and with counterbores to differentdepths (plots 220,222,224,226 show increasing depths of counterbore) aswell as with no counterbore (namely an internal diameter of 3.6 mm forthe full depth-plot 228).

Adding a counterbore to the open end of the component reduces the amountof friction and creates a short term pressure rise in the initial partof the liquid pressure profile as the ram rides over the shoulderbetween the different bore diameters. The deeper the counterbore, thenearer this pressure rise is to the main peak. This measure can thus beused to increase the peak pressure, and indeed in plot 226, the depth ofthe shoulder is such that the main pressure peak is increased.

FIG. 8 shows a shock absorber open at both ends and in which threedifferent internal diameters d1, d2 and d3 are provided. The componentis initially provided with a bore of diameter d2, and an additionalcounterboring step provides the increased internal diameter of d1 to adesired depth from the ram side of the component and an additionalcounterboring step provides the increased internal diameter of d3 to adesired depth from the piston side of the component. As in FIG. 6, d1can equal 3.77 mm and d2 can equal 3.6 mm for a ram diameter of 4.0 mm.The depths and diameters of the counterbores from both ends willinfluence the pressure profile characteristics.

FIG. 9 shows comparative pressure profiles for an injector with no shockabsorbing component (plot 200), for a component with no counterbore(namely an internal diameter of 3.6 mm for the full depth-plot 228 as inFIG. 7), and for components which differ only in the diameter of thepiston side bore (plots 230,232,234,236 are for successively increasingvalues of d3). The plot closest to the original plot with no shockabsorber is plot 236, and this is for a design in which the piston sidecounterbore is larger in diameter than the ram. This section of theshock absorber thus provides no additional resistance to the movement ofthe ram towards the piston, but does ensure that the low pressure in thedrug is maintained for a suitable time period to enable slow bubblecollapse. The plot 236 is for a component with d1=3.77 mm, d2=3.6 mm,d3=4.05 mm.

Designs with a rib as shown in FIG. 8 are found to provide the bestcombination of pressure profiles. The counterbore on the ram side of thecomponent provides a step increase in pressure (shown as 240 in FIG. 9)which then drops, but a low pressure is maintained for gradual bubblecollapse. The counterbore on the piston side reduces the amount offriction, thereby reducing the loss of peak pressure resulting from thepresence of the shock absorbing component.

To anyone skilled in the art, it is clear that there are many methods ofcausing a gradual increase in pressure in a fluid constrained by apiston. Any component which reduces the initial pressure surge can beused, and there are many compressible elements which may be appropriatefor this purpose. Whilst the invention has been shown as an improvementto one specific known design of needleless injector, the invention canbe applied to many different designs, and one example only has beengiven above. In particular, there are many different ways of releasingstored energy to apply a force to the ram, other than the gas springshown in the specific example.

The shock absorbing component may comprise part of the piston or theram, or as in the example above it may effectively be defined by theinteraction of these two components. The shock absorbing could also beapplied to the output of the source of energy for driving the ram. Theinvention essentially provides any means for controlling the speed ofbubble collapse within the liquid.

In another example, the internal opening of the cylindrical shockabsorbing component can be greater in diameter than the diameter of theram, and the ram can be coupled to the inner wall of the shock absorbingcomponent through a grease which allows transfer of force, such asgrease made by the company Kilopoise.

In the example above, the component is machined, and there are stepchanges in the internal diameter using counterboring techniques. Theremay instead be tapered changes to the internal diameter—for example thediameter of the opening in the cylinder may increase or decrease alongthe length of the component, or else a central rib may be defined, butwith a taper to the larger opening size at the ends. This is of coursemore easily implemented for a moulded component.

Instead of the ram sliding through the shock absorbing component, it maypush against it, for example it may be a rubber coupling member.

The term “shock absorbing means” has been used for the component of theinvention, as it provides an initial lower pressure time period withinthe liquid before the main transfer of force from the ram to the piston.This is achieved by using some of the force (shock) from the ram. Itcould equally be described as means for providing an initial time periodof relatively low pressure within the liquid before the main transfer offorce from the ram to the piston. The term.“shock absorbing means” isintended to cover all of these possibilities, including theimplementation of the shock absorption by modification to the energysource (e.g. compressed gas source).

1. A needleless injector comprising: a syringe body having an opening atone end; a piston housed within the syringe body for urging a liquidwithin the syringe body through the opening; a ram for driving thepiston; means for applying a force to the ram; and means for reducing aninitial transfer of force from the ram to the piston.
 2. The injector ofclaim 1, wherein the force-reducing means comprising a componentassociated with the ram and/or the piston.
 3. The injector of claim 2,wherein the force-reducing means comprises a cylinder, in which an endof the ram is slidably received.
 4. The injector of claim 3, wherein thecylinder forms part of the piston.
 5. The injector of claim 3, whereinthe cylinder is closed at one end, the closed end lying adjacent thepiston, and wherein the ram is received adjacent the open end of thecylinder before the application of force to the ram.
 6. The injector ofclaim 3, wherein the cylinder is open at both ends.
 7. The injector ofclaim 6, wherein the internal opening of the cylinder has a constantinternal diameter.
 8. The injector of claim 6, wherein the internalopening of the cylinder has at least two internal diameters, a firstinternal diameter at an end of the cylinder for cooperation with theram, and a second smaller internal diameter.
 9. The injector of claim 8,wherein the internal opening of the cylinder has three internaldiameters, a third internal diameter at an end of the cylinder forcooperation with the piston, the third internal diameter being greaterthan the second internal diameter.
 10. The injector of claim 9, whereinthe third internal diameter is equal to or greater than the diameter ofthe ram.
 11. The injector of claims 3, wherein the cylinder has a lengthof between 1 mm and 5 mm.
 12. The injector of claims 3, wherein the ramis slidably received in the cylinder with a fluid tight fit.
 13. Theinjector of claim 1, wherein the force-reducing means comprises acompressible member.
 14. The injector of claim 1, wherein the means forapplying a force to the ram comprises a source of pressurized gas.
 15. Amethod of delivering liquid from a needleless injector syringe whichcomprises a piston housed within a syringe body and a ram for drivingthe piston thereby causing liquid to be driven out of the syringe, themethod comprising: applying an initial force to the ram to initiatedelivery of the liquid; during a first stage of the delivery reducingthe initial force applied to the ram and applying the reduced force tothe piston; and during a second stage of the delivery, transferring asubstantial portion of the initial force applied to the ram to thepiston.
 16. The method of claim 15, wherein the initial force applied tothe ram is reduced in the first stage by spacing the ram from thepiston, the spacing being reduced during the first stage.
 17. The methodof claim 16, wherein when the spacing is reduced during the first stage,the movement of the ram towards the piston causes compression of aclosed volume of gas.
 18. A needleless injector comprising: a syringebody having an opening at one end; a piston housed within the syringebody for urging a liquid within the syringe body through the opening; aram for driving the piston; means for applying a force to the ram; andmeans for controlling the speed of bubble collapse within the liquid.19. The injector of claim 18, wherein the pressure in the syringe bodyincreases to a pressure of about 1 to about 5 Mpa upon applying a forceto the ram.
 20. The injector of claim 18, wherein the size of a bubblepresent within the liquid collapses to about {fraction (1/20)} or lessof an original size.
 21. The method of claim 15, wherein, during thefirst stage of the delivery, the pressure within the syringe bodyincreases to a pressure of about 1 to about 5 Mpa.
 22. The method ofclaim 21, wherein the increase in pressure occurs within 200 μs.